Chao Sheng Liao

Cost-effectiveness analysis for determining optimal cut-off of immunochemical faecal occult blood test for population-based colorectal cancer screening (KCIS 16)

Objectives: We aimed to determine the optimal cut-off of the immunochemical faecal occult blood test (iFOBT) by using cost-effectiveness analysis. Methods: A total of 22,672 subjects aged 50 years or older were invited to have an uptake of iFOBT. We collected data from screen-detected cases for the cut-off above 100 ng/mL and obtained interval cancers from a nationwide cancer registry for a cut-off below 100 ng/mL. We found a total of 65 colorectal cancer (CRC) cases, including 43 detected by screen and 22 diagnosed between screens (interval cases). The optimal cut-off was first determined by receiver operating characteristics (ROC) curve analysis. Formal economic evaluation was further applied to identifying the optimal cut-off by assessing the minimum incremental cost-effectiveness ratio (ICER), an indicator for cost per life year gained (effectiveness), given a series of cut-offs of iFOBT, ranging from 30 to 200 ng/mL compared with no screening. Results: ROC curve analysis found the optimal cut-off of iFOBT to be 100 ng/mL at which the sensitivity, false-positive and odds of being affected given a positive result were 81.5% (70.2%–89.2%), 5.7% (5.4%–6.0%) and 1.24 (1.19–1.32), respectively. The area under ROC curve was 0.87 (0.81–0.93). In economic appraisal, the screening programme irrespective of any cut-off dominated (less cost and more effectiveness) over the control group. The optimal cut-off (the lowest ICER) was 110 ng/mL at which an average of 0.054 life year was gained and that of 950 (

Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program

US) was saved. Conclusions: We used cost-effectiveness to identify 110 ng/mL as the optimal cut-off of iFOBT in a Taiwanese population-based screening for CRC. Our model provides a useful approach for health policy-makers in designing population-based screening for CRC to determine the optimal cut-off of iFOBT when cost and effectiveness need to be taken into account.

Baseline faecal occult blood concentration as a predictor of incident colorectal neoplasia: longitudinal follow-up of a Taiwanese population-based colorectal cancer screening cohort

The effectiveness of fecal immunochemical testing (FIT) in reducing colorectal cancer (CRC) mortality has not yet been fully assessed in a large, population‐based service screening program.

Evaluation of abdominal ultrasonography mass screening for hepatocellular carcinoma in Taiwan

BACKGROUND Despite widespread use of the immunochemical faecal occult blood test (iFOBT), little is known about the subsequent risk of developing colorectal neoplasia for participants with negative iFOBT results. We investigated whether the concentration of faecal haemoglobin at the first screen is predictive of the subsequent incidence of colorectal neoplasia in those with a negative screening result. METHODS Between 2001 and 2007, we did a prospective cohort study within the Keelung community-based iFOBT screening programme for residents aged 40-69 years, using a cutoff faecal haemoglobin concentration of 100 ng/mL to classify attendees as negative and positive groups for further clinical investigations. 44,324 participants with negative findings and 1668 with a positive result at the first screen (854 non-referrals who refused colonoscopy and 814 with a false-positive result as assessed by colonoscopy) were followed up to ascertain cases of colorectal neoplasia. We investigated the association between baseline faecal haemoglobin concentration and risk of incident colorectal neoplasia, after adjusting for possible confounders. FINDINGS Median follow-up was 4·39 years (IQR 2·53-6·12) for all 45 992 participants, during which the incidence of colorectal neoplasia increased from 1·74 per 1000 person-years for those with baseline faecal haemoglobin concentration 1-19 ng/mL, to 7·08 per 1000 person-years for those with a baseline concentration of 80-99 ng/mL. The adjusted hazard ratios (HRs) increased from 1·43 (95% CI 1·08-1·88) for baseline faecal haemoglobin concentration of 20-39 ng/mL, to 3·41 (2·02-5·75) for a baseline concentration of 80-99 ng/mL (trend test p<0·0001), relative to 1-19 ng/mL. These results did not change when we included repeated iFOBT measurements. Non-referrals had the highest risk of incident colorectal neoplasia (adjusted HR 8·46 [6·08-11·76]). INTERPRETATION Quantitative faecal haemoglobin concentration at first screening predicts subsequent risk of incident colorectal neoplasia. During follow-up, risk stratification based on faecal haemoglobin could help clinicians, with particular attention being paid to those with higher initial faecal haemoglobin concentrations, especially those just under the threshold taken to indicate presence of colorectal neoplasia. FUNDING None.

Impact of faecal haemoglobin concentration on colorectal cancer mortality and all-cause death

Mass screening with abdominal ultrasonography (AUS) has been suggested as a tool to control adult hepatocellular carcinoma (HCC) in individuals, but its efficacy in reducing HCC mortality has never been demonstrated. This study aimed to assess the effectiveness of reducing HCC mortality by mass AUS screening for HCC based on a program designed and implemented in the Changhua Community‐based Integrated Screening (CHCIS) program with an efficient invitation scheme guided by the risk score. We invited 11,114 (27.0%) of 41,219 eligible Taiwanese subjects between 45 and 69 years of age who resided in an HCC high‐incidence area to attend a risk score‐guided mass AUS screening between 2008 and 2010. The efficacy of reducing HCC mortality was estimated. Of the 8,962 AUS screening attendees (with an 80.6% attendance rate), a total of 16 confirmed HCC cases were identified through community‐based ultrasonography screening. Among the 16 screen‐detected HCC cases, only two died from HCC, indicating a favorable survival. The cumulative mortality due to HCC (per 100,000) was considerably lower in the invited AUS group (17.26) compared with the uninvited AUS group (42.87) and the historical control group (47.51), yielding age‐ and gender‐adjusted relative mortality rates of 0.69 (95% confidence interval [CI]: 0.56‐0.84) and 0.63 (95% CI: 0.52‐0.77), respectively. Conclusion: The residents invited to community‐based AUS screening for HCC, compared with those who were not invited, showed a reduction in HCC mortality by ∼31% among subjects aged 45‐69 years who had not been included in the nationwide vaccination program against hepatitis B virus infection. (Hepatology 2014;59:1840–1849)

Community-based multiple screening model: Design, implementation, and analysis of 42,387 participants taiwan community-based integrated screening group

Objective To assess the effect of an incremental increase in faecal haemoglobin (f-Hb) concentration on colorectal cancer (CRC) mortality and all-cause death. Design We conducted an observational study of cohorts over time based on two population-based CRC screening programmes. Setting Two cities of Taiwan. Participants 1233 individuals with CRC (217 prevalent cases and 1016 incident cases) and 2640 with colorectal adenoma (1246 prevalent cases and 1394 incident cases) found in the two cohorts of 59 767 and 125 976 apparently healthy individuals, aged 40 years and above, who had been invited to participate in screening since 2001 and 2003, respectively. Main outcome measures Death from CRC and all-cause death ascertained by following up from the entire two cohorts over time until 2009. Results The effect of an incremental increase in f-Hb on the risk for CRC mortality was noted, increasing from a slightly increased risk for the category of f-Hb of 20–49 ng Hb/mL (adjusted HR (aHR)=1.09; 95% CI 0.68 to 1.75) to 11.67 (95% CI 7.71 to 17.66) for the group with f-Hb≥450 ng Hb/mL as compared with the group considered baseline with f-Hb of 1–19 ng Hb/mL (p<0.001). A similar but less marked increasing trend was found for all-cause mortality, aHR increasing from 1.15 (95% CI 1.07 to 1.24) for the group with f-Hb of 20–49 ng Hb/mL to 1.67 (95% CI 1.54 to 2.07) for the group with f-Hb≥450 ng Hb/mL. Conclusions We substantiated the impacts of an incremental increase in f-Hb on the risk for death from CRC and all-cause death, consistently showing a significant gradient relationship. Both discoveries suggest that f-Hb may not only make contribution to facilitating individually tailored screening for CRC but also can be used as a significant predictor for life expectancy.

Prognosis of small hepatocellular carcinoma treated by percutaneous ethanol injection and transcatheter arterial chemoembolization

Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow‐up.

A new insight into fecal hemoglobin concentration-dependent predictor for colorectal neoplasia

This study was conducted to assess the progression and prognosis of a total of 108 patients with hepatocellular carcinoma (HCCs) smaller than 5 cm in diameter treated by percutaneous ethanol injection (PEI) with or without transcatheter arterial chemoembolization. All patients were classified as Child-Pugh A (n = 84) or B (n = 24). Logarithm of hazard rate (per month) with time since therapy was assessed. The Weibull model was used to elucidate the effect of pretreatment clinico-pathologic variables on prognosis. The rate of death increased by 4.7% (95% CI: 3.7-5.7%) per month since treatment. Child-Pugh B status was associated with a 2.8-fold risk (95% CI: 1.52-5.16) of death. Those with a high level of AST or alcoholic cirrhotics had a two-fold risk (95% CI:1.14-3.42) for death from HCC. Our results suggest the optimal frequency of clinical surveillance of small HCC cases after treatment should take account of increased hazard rate with time and the roles of pretreatment clinico-pathologic variables.

Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions

We sought to assess how much of the variation in incidence of colorectal neoplasia is explained by baseline fecal hemoglobin concentration (FHbC) and also to assess the additional predictive value of conventional risk factors. We enrolled subjects aged 40 years and over who attended screening for colorectal cancer with the fecal immunochemical test (FIT) in Keelung community‐based integrated screening program. The accelerated failure time model was used to train the clinical weights of covariates in the prediction model. Datasets from two external communities were used for external validation. The area under curve (AUC) for the model containing only FHbC was 83.0% (95% CI: 81.5–84.4%), which was considerably greater than the one containing only conventional risk factors (65.8%, 95% CI: 64.2–67.4%). Adding conventional risk factors did not make significant additional contribution (p = 0.62, AUC = 83.5%, 95% CI: 82.1–84.9%) to the predictive model with FHbC only. Males showed a stronger linear dose‐response relationship than females, yielding gender‐specific FHbC predictive models. External validation confirms these results. The high predictive ability supported by a dose‐dependent relationship between baseline FHbC and the risk of developing colorectal neoplasia suggests that FHbC may be useful for identifying cases requiring closer postdiagnosis clinical surveillance as well as being an early indicator of colorectal neoplasia risk in the general population. Our findings may also make contribution to the development of the FHbC‐guided screening policy but its pros and cons in connection with cost and effectiveness of screening should be evaluated before it can be applied to population‐based screening for colorectal cancer.

Remission, Relapse, and Metastasis/death of Small Hepatocellular Carcinoma Treated with Percutaneous Ethanol Injection

Objective Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions. Design Cross-sectional design. Setting Hospital-based and community-based screening settings. Participants A hospital-based deviation cohort of 3172 participants to evaluate test performance and a community-based validation cohort of 3621 to verify the findings. Interventions Three types of stool tests with bidirectional endoscopy as the reference standard. Outcomes Sensitivity, specificity and positive and negative likelihood ratios. Results For detecting upper gastrointestinal lesions in cases with negative immunochemical tests, the sensitivity, specificity, and positive and negative likelihood ratios of the guaiac-based and H pylori antigen tests were 16.3% (95% CI 13.3% to 19.8%), 90.1% (88.9% to 91.2%), 1.64 (1.31 to 2.07), and 0.93 (0.89 to 0.97), respectively, and 52.5% (48.1% to 56.9%), 80.6% (79.0% to 82.1%), 2.71 (2.41 to 3.04) and 0.59 (0.54 to 0.65), respectively. For detecting upper gastrointestinal lesions in cases with normal colonoscopy, the results of the guaiac-based and H pylori antigen tests were 17.9% (14.8% to 21.5%), 90.1% (88.9% to 91.2%), 1.81 (1.45 to 2.26) and 0.91 (0.87 to 0.95), respectively, and 53.1% (48.6% to 57.4%), 80.7% (79.1% to 82.2%), 2.75 (2.45 to 3.08) and 0.58 (0.53 to 0.64), respectively. Within the community, positive predictive values of the immunochemical and H pylori antigen tests were 36.0% (26.0% to 46.0%) and 31.9% (28.3% to 35.5%), respectively, for detecting lower and upper gastrointestinal lesions, which were similar to expected values. Conclusions The H pylori stool antigen test is more accurate than the guaiac-based test in the screening of upper gastrointestinal lesions in a population with high prevalence of H pylori infection and upper gastrointestinal lesions. It is applicable to add the H pylori antigen test to the immunochemical test for pan detection. Trial registration NCT01341197 (ClinicalTrial.gov).